The nucleoprotein (NP) gene, but not the M gene, of the A/Pintail/119/79 avian influenza A virus specifies attenuation in monkeys. The PB2 gene also contributes to attenuation, but the restriction of replication specified by this gene can be modified by the presence of other avian or human influenza A virus genes. A reassortant lacking the attenuating NP and PB2 avian influenza virus genes, but containing the other four avian influenza A virus genes was also attenuated in monkeys. Thus, genes other than NP and PB2 can also contribute to the attenuation phenotype. The infectious dose-50 of an avian-human influenza A virus reassortant virus for squirrel monkeys was comparable when delivered by either aerosol or intranasal route. This suggests that the aerosol route of administration of viruses that are restricted in their replication in the lungs has little advantage over the intranasal route. Bovine parainfluenza virus type 3 is attenuated for chimpanzees and induces a high level of resistance to infection with human parainfluenza type 3 virus in squirrel monkeys. These observations suggest that the bovine parainfluenza type 3 virus may prove to be useful in immunization against human parainfluenza type 3 virus disease during infancy and early childhood.